The hypothesis that brain-derived neurotrophic factor (BDNF) is involved in the pathogenesis of major depression is supported by several research findings; however, genetic studies assessing the relationship between BDNF and psychiatric disorders have produced conflicting results.We examined the effect of a BDNF polymorphism on depression susceptibility in MexicanAmericans.The single nucleotide polymorphism (Val66Met), which has been shown to have functional and behavioral effects, was genotyped in 284 depressed participants and 331 controls, showing association with depression (P=0.005). Individuals homozygous for the major allele (GG) had an increased chance of being depressed (OR=1.7 95% CI 1.17-2.47).Our findings support the association of BDNF single nucleotide polymorphism rs6265 and depression, suggesting that this polymorphism may increase susceptibility to major depression in Mexican-Americans.

Cross-cultural investigation in psychiatry is revealing the need for standardised instruments in diagnosing and assessing depression. Recently, a new instrument was developed to evaluate depressed patients, namely the Montgomery-Asberg Depression Rating Scale (MADRS). The present study introduced the MADRS in Brazil, comparing it to the Hamilton Depression Rating Scale, the Visual Analogue Mood Scale (a self-rating scale), and with the global clinical assessment of independent Brazilian psychiatrists. The results show correlation between MADRS and the three other assessments, indicating that it is a useful and operational instrument to evaluate depressed patients. They also support the application of the MADRS in cross-cultural studies of depression in Brazil and other countries. These results are critically discussed.

Cyclic nucleotide phosphodiesterases (PDEs) hydrolyze the intracellular second messengers cAMP and cGMP to their corresponding monophosphates. PDEs play an important role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. We have previously shown that the individual haplotype GAACC in the PDE11A gene was associated with major depressive disorder (MDD) based on block-by-block analysis. There are two PDE genes, PDE11A and PDE1A, located in chromosome 2q31-q32. In this study, we have further explored whether the whole region 2q31-q32 contribute to MDD or antidepressant response 278 depressed Mexican-American participants and 321 matched healthy controls. Although there is no signifi cant interaction between the two genes, the remission rate of individual carrying the combination genotype at rs1880916 (AG/AA) and rs1549870 (GG) is signifi cantly increased. We analyzed the global haplotype by examining 16 single-nucleotide polymorphisms (SNPs) in PDE11A and six SNPs in PDE1A. None of the haplotypes consisting of six SNPs in the PDE1A have a signifi cant difference between depressed and control groups. Among haplotypes consisting of 16 SNPs across 440 kb in the PDE11A gene, 18 common haplotypes (with frequency higher than 0.8%) have been found in the studied population. Six haplotypes showed signifi cantly different frequencies between the MDD group and the control group. The phylogenetic network result for the 16 SNPs showed that several historic recombination events have happened in the PDE11A gene. The frequency of one haplotype is signifi cantly lower in the remitter group than in the nonremitter group for the depressed participants treated with either desipramine or fl uoxetine. Thus, our data suggest that the PDE11A global haplotype is associated with both MDD and antidepressant drug response.

Background: The mechanisms underlying food choices are complex and involve neuroendocrine and biochemical signaling. Among neuroendocrine signals, leptin may play a prominent role in food preference. Objective: This study was designed to obtain an understanding of the effects of leptin replacement on macro-and micronutrient preferences in leptin-deficient adults. Design: We studied the effects of leptin replacement on three adults with genetic leptin deficiency during the initial 12 months of treatment. Dietary intake was measured in our study by weighed food consumption records. Nutrient intake was calculated using a nutrition analysis software. Results: After leptin replacement was started, all patients had initially a marked reduction in food intake. The reduction in caloric intake differentially affected intake of macro-and micronutrients. There was an initial shift toward a higher percentage consumption of fats and a decrease in the intake of carbohydrates. Significant differences also occurred in 7 distinct types of macronutrients, 12 vitamins, 11 minerals and 1 amino acid. Conclusions: We documented several specific leptin-induced changes in macro-and micronutrients intake during the course of leptin-replacement treatment, the majority of which were not related to the decrease in total caloric consumption.

To the Editors:Restless legs syndrome (RLS) is a neurological disorder characterized by irresistible movements and dysesthetic sensations in the legs. Its prevalence in general population epidemiological studies is 5% to 10%. 1 Drug-induced RLS, although now a recognized entity, remains an underdiagnosed etiology of secondary RLS. Selective serotonin reuptake inhibitors have long been known to exacerbate RLS, and it has anecdotally been described with atypical antipsychotics. 2-5 However, there are no reports of clozapine-induced RLS in literature. A case of RLS associated with clozapine is described. The underlying pathophysiological mechanism of this presentation is discussed.Mr A, a 26-year-old man, was diagnosed with bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) with a 6-year duration. During one of the manic episodes, he developed severe extrapyramidal symptoms characterized by tremors, bradykinesia, and sialorrhea while on haloperidol 20 mg/d and valproate 1400 mg/d. Subsequently, haloperidol was replaced by clozapine 25 mg/d, which was increased to 50 mg/d over the next 2 days, whereas valproate was continued at the same dose. On the third day of treatment with clozapine (at 50 mg/d), he started experiencing unpleasant sensations in his calves and burning sensation over his feet. These occurred only when he lay in bed at night and would be relieved by moving the legs or walking but would recur on lying in bed. He had initial and middle insomnia. Mr A denied having these symptoms during the daytime. Considering that this may be akathisia, lorazepam (2 mg) was added at bedtime. However, he continued to exhibit the same symptoms, but only at night. Two days later, clozapine was stopped; and that night, Mr A did not experience any uncomfortable sensations or movements of his legs. A week later, the patient agreed to a retrial of clozapine manufactured by a different pharmaceutical company. However, he again developed the same symptoms at night. Subsequently, clozapine was replaced by olanzapine titrated up to 20 mg/d without reemergence of the above symptoms. The dose of valproate remained unchanged throughout the course of treatment. Family history revealed that the patient's father had evidence to suggest idiopathic RLS. The patient's neurological examination was unremarkable. Laboratory investigations including serum iron, ferritin, glucose, thyroid-stimulating hormone, and renal function tests were within normal limits. Because of the transient nature and drug-related origin of the abnormal movement, the patient did not consent to polysomnography.This patient met the diagnostic criteria for RLS. 6 Unfortunately, polysomnography data were not available to diagnose or exclude comorbid periodic leg movements in sleep. Akathisia was ruled out on the basis of the presence of dysesthesias in the legs rather than internal restlessness, worsening of symptoms at night, accompanying sleep disturbance, and positive family history. 5,7 A PubMed search done on J...